UMLS:C0020538 - FACTA Search

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Query: UMLS:C0020538 (hypertension)
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Ramipril is safe and effective in the treatment of hypertension and heart failure, but this is not reviewed here. Ramipril is a lipophilic angiotensin-converting enzyme inhibitor suitable for once-daily administration. In addition to decreasing angiotensin II and increasing bradykinin levels, ramipril increases the levels of vasodilatory renal medullary neutral lipids and inhibits platelet-derived growth factor-induced proliferation of glomerulus cells. Ramipril also decreases transforming growth factor-beta in the kidney. Changes in kidney structure and proteinuria are characteristics of the streptozotocin (STZ) rat model of diabetes, and these are prevented by ramipril. In STZ diabetes, doses of ramipril that have no effect on blood pressure reverse vascular hypertrophy. In animal models of kidney failure (subtotal nephrectomy, stroke-prone spontaneously hypertensive rats), ramipril is renoprotective and some of this renoprotective effect is independent of blood pressure lowering. In humans, clinical doses of ramipril probably do not modify glucose metabolism but do reduce the levels of LDL- and HDL-cholesterol. In clinical trials of renal effects, ramipril has been shown to increase cortical nephron flow in hypertension and to reduce proteinuria in patients with and without diabetes and/or hypertension. Some of the smaller clinical trials showed beneficial effects on kidney function with low doses of ramipril that do not lower blood pressure. A large clinical trial in nondiabetic proteinuria, the Ramipril Efficacy in Nephropathy (REIN) trial, has shown that ramipril 1.25 mg/day, which does not lower blood pressure, arrested the decline in glomerular filtration rate and prolonged the time to end-stage renal failure. In diabetic patients who have had a previous cardiovascular event or having one other cardiovascular risk factor, the MICRO-HOPE clinical trial showed that ramipril lowers the combined risk of myocardial infarction, stroke and cardiovascular death by 25%. In conclusion, ramipril has proven beneficial effects in kidney disease alone or in association with diabetes and in diabetes without kidney disease, and is the pril for diabetes and kidney disease. (c) 2001 Prous Science. All rights reserved.
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PMID:Is Ramipril the pril for diabetes and kidney disease? 1276 20

Costs of providing a particular medical service can be measured, but it is more difficult to assess whether the service provides good value for the money spent. Rigorous trials have demonstrated the health benefits connected with interventions for treatment and prevention of cardiovascular disease (CVD), and in-depth analyses of the costs associated with many of those interventions have been performed. Careful use of terminology clearly differentiating among cost-minimization (relative costs of proved equivalent therapeutics), cost-effectiveness (lives saved or years of life added), and cost-benefit (total net effect in monetary terms) analyses is warranted. Although trials commonly assess clinical effectiveness as reductions in mortality or CVD-specific outcomes, improvement in quality of life may be equally important and is expressed in quality-adjusted life-years. Comparisons between therapies can be assessed as a cost-effectiveness ratio. Extensive cost-effectiveness studies have been conducted on many important cardiovascular therapies: (1) beta-blockers and diuretics for multiple CVD outcomes, mortality, and prevention of recurrent myocardial infarction (MI); (2) statins for both primary and secondary prevention of CVD; (3) enalapril for prevention and treatment of congestive heart failure; (4) tissue plasminogen activator treatment of acute MI; (5) coronary artery bypass graft for left main, single-, and 2-vessel coronary artery disease, or severe angina; (6) physician counseling for smoking; and (7) radiofrequency ablation therapy for Wolff-Parkinson-White syndrome. Therapies considered economically attractive include (1) secondary prevention with statins in hyperlipidemia, (2) smoking cessation programs, (3) primary prevention in treatment of high blood pressure with diuretics and beta-blockers, (4) primary prevention with regular exercise programs, (5) secondary prevention with cardiac rehabilitation, and (6) postinfarction treatment with beta-blockers and angiotensin-converting enzyme (ACE) inhibitors. A recent cost-minimization analysis has been performed showing aspirin to be a "best buy" therapy for secondary prevention of CVD. The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) and Telmisartan Randomized Assessment Study in ACE-I Intolerant Patients with Cardiovascular Disease (TRANSCEND) program provide potential opportunities for both cost-minimization and cost-effectiveness analyses.
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PMID:How cost-effective are new preventive strategies for cardiovascular disease? 1278 5

This longitudinal prospective study was designed to assess the effects of the angiotensin converting enzyme inhibitor (ACEI) ramipril on ventricular mass, left ventricle (LV) diastolic function and blood pressure in patients with mild to moderate essential hypertension and hyperinsulinemia. LV diastolic dysfunction is the first target organ alteration occurring in hypertensive patients, while ventricular hypertrophy is the most relevant predictive factor for cardiovascular morbility and mortality in systemic hypertension. Because several studies have demonstrated that there is no direct correlation between blood pressure values and the severity of LV hypertrophy or diastolic dysfunction, it is assumed that other factors are involved in the genesis of these functional alterations. Moreover, the hypertensive effect of insulin is caused by sympathetic stimulation, sodium and water renal retention and protooncogene stimulation leading to myocardial and vascular fibrosis and hypertrophy. We studied 24 hypertensive patients with hyperinsulinemia. All patients underwent an overall and cardiologic clinical evaluation, and electrocardiographic and ecocardiographic studies were performed at baseline and 6 months after being treated with 2.5 to 5 mg/day ramipril. Ramipril treatment significantly reduced systolic (12 mmHg) and diastolic (12 mmHg) pressure levels, basal insulin serum levels (23.62 pmol/dL vs 10.42 pmol/dL), and left ventricle mass index values (143.8 g/m2 vs 118.2 g/m2). Among the variables assessing LV diastolic function, only the transmitral flow E/A wave ratio showed significant differences in women. Ramipril was well tolerated and no significant adverse events were reported.
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PMID:[Effect of ramipril on the glucose/insulin coefficient and the ventricular mass index in patients with light to moderate arterial hypertension]. 1282 Apr 91

Angioneurotic edema is a rare (0.1-0.2%) but potentially life-threatening side effect of angiotensin-converting enzyme inhibitors. It can result in serious respiratory distress, airway obstruction and death. Angiotensin-converting enzyme inhibitors associated angioedema is clinically poorly recognized and frequently underestimated condition. A case history of patient with angioneurotic edema due to treatment with ramipril is presented. A 51-year-old man has been sequentially treated for two years with atenolol, indapamide, enalapril, and fosinopril due to primary arterial hypertension. When the treatment was switched to ramipril 5 mg twice a day the fourth dose of the drug was followed by swelling of lips, tongue, and pharynx without symptoms of airway obstruction. Ramipril was discontinued, prednisolone 120 mg and loratidine 10 mg were given. Symptoms of angioedema gradually disappeared. Mechanisms of angioedema are not fully clear. Pharmacological action of angiotensin-converting enzyme inhibitors on bradykinin and substance P, immunological mechanisms and disarrangements in complement system are discussed. Treatment includes immediate withdrawal of angiotensin-converting enzyme inhibitors and acute therapy with epinephrine 0.3-0.5 ml subcutaneous, 50 mg diphenhydramine s/c or i/v, 40-50 mg methylprednisolone. Future treatment with angiotensin-converting enzyme inhibitors is contraindicated.
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PMID:[Tongue angioedema associated with angiotensin-converting enzyme inhibitor (diagnosis, differential diagnosis, treatment)]. 1282 80

Hypertension in combination with clinically overt diabetes mellitus is recognized as a particularly powerful combination of risk factors that greatly increases cardiovascular vulnerability. There is also evidence that presumed pre-diabetic conditions such as insulin resistance, hyperinsulinaemia and compensatory hyperglycaemia may amplify overall cardiovascular risk in patients with hypertension, especially when encountered as part of the condition known as metabolic syndrome X (Reaven's syndrome). The long-term benefits of antihypertensive therapy may be compromised if these drugs exert adverse effects on metabolic parameters such as insulin sensitivity, or if they promote a transition from pre-diabetes to overt diabetes. Class differences in the effects of antihypertensives on metabolic indices may therefore be an important consideration when choosing treatment for patients who exhibit these characteristics. Experience from clinical trials suggests that drugs that target the renin-angiotensin system may have metabolic advantages over drugs such as beta-blockers and diuretics, but this conclusion has not been proved definitively. Moxonidine, which selectively targets imidazoline type-1 receptors in the sympathetic vasomotor centres of the rostral-ventrolateral medulla, is an effective antihypertensive and has been reported to exert favourable metabolic effects in preclinical and clinical studies. The MARRIAGE study (Moxonidine And Ramipril Regarding Insulin And Glucose Evaluation) will extend these preliminary observations by comparing the effects of moxonidine and the ACE inhibitor ramipril--and the combination of both drugs--on metabolic and haemodynamic parameters in patients with hypertension and impaired fasting glycaemia. A description is provided of the design and conduct of MARRIAGE.
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PMID:Selective imidazoline agonist moxonidine plus the ACE inhibitor ramipril in hypertensive patients with impaired insulin sensitivity: partners in a successful MARRIAGE? 1502 45

Hypertension is one of the most important modifiable risk factors for cardiovascular pathology, such as atherosclerosis and cardiac left ventricular hypertrophy, including acute events such as stroke and myocardial infarction (MI). In particular, the risk of ischaemic and haemorrhagic stroke is directly and continuously related to high blood pressure levels. The renin-angiotensin system (RAS) plays an important role in volume homeostasis and blood pressure regulation. It also helps to prevent cell and organ damage from ischaemia during acute volume loss. However, angiotensin-II (A-II)--the main effector peptide of the RAS--also exerts a number of pathological effects, which are mediated by the AT 1 receptor. The Ongoing Telmisartan Alone and in Combination with Ramipril Global End point Trial (ONTARGET) programme consists of two parallel trials where ONTARGET as a large, long-term study compares the efficacy of the angiotensin-receptor antagonist, telmisartan, the renin-angiotensin-converting enzyme (ACE) inhibitor, ramipril and combination therapy with telmisartan plus ramipril for reducing cardiovascular and cerebral risk. Telmisartan, due to its long duration of action, compares favourably with other angiotensin-receptor antagonists. In the Heart Outcomes Prevention Evaluation (HOPE) study, ramipril was shown to reduce the risk for MI and other cardiovascular events in patients at high risk for pathological cardiac events, but without heart failure or a low ejection fraction. The cardiovascular outcomes of high-risk patients using the same criteria as those of the HOPE study will be assessed in both trials. TRANSCEND differs from ONTARGET in that this trial will enrol patients who do not tolerate ACE inhibitors. This parallel study will therefore be able to compare telmisartan and placebo treatment. Both ONTARGET and TRANSCEND trials feature the same primary composite end point: death caused by cardiovascular disease, acute MI, stroke and hospitalisation because of congestive heart failure. The secondary end points will focus on reductions in the development of Type 2 diabetes mellitus, nephropathy, cognitive decrease and dementia as well as atrial fibrillation.
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PMID:Challenges in improving prognosis and therapy: the Ongoing Telmisartan Alone and in Combination with Ramipril Global End point Trial programme. 1515 18

Mechanisms underlying biological effects of statin and angiotensin-converting enzyme inhibitor therapies differ. Thus, we studied vascular responses to combination therapy in hypercholesterolemic patients. A randomized, double-blind, placebo-controlled, crossover trial was conducted with 50 hypercholesterolemic patients with simvastatin and either placebo or ramipril (study I) and in 45 hypercholesterolemic diabetic patients with simvastatin or ramipril with placebo or simvastatin combined with ramipril (study II) for 2 months with 2 months washout. In study I simvastatin combined with ramipril significantly reduced blood pressure after 2 months. Simvastatin alone or combined with ramipril significantly changed lipoproteins, improved percent flow-mediated dilator response to hyperemia by 30+/-5% and 53+/-6%, respectively (P<0.001), and reduced plasma levels of malondialdehyde by 4+/-7% (P=0.026) and 25+/-4% (P<0.001), respectively. Monocyte chemoattractant protein-1 levels decreased by 3+/-3% and 12+/-2%, respectively (P=0.049 and P=0.001, respectively), C-reactive protein levels changed by 0% and 18%, respectively (P=0.036 and P<0.001, respectively), and plasminogen activator inhibitor-1 antigen levels changed by -7+/-7% and 17+/-5%, respectively (P=0.828 and P<0.001, respectively). In study II ramipril alone did not significantly change lipoproteins and C-reactive protein levels, however, simvastatin combined with ramipril significantly changed lipoproteins and C-reactive protein levels more than ramipril alone (P<0.001 and P=0.048 by ANOVA, respectively). Ramipril alone or simvastatin combined with ramipril significantly improved the percent flow-mediated dilator response to hyperemia (both P<0.001), however, simvastatin combined with ramipril showed significantly more improvement than ramipril alone (P<0.001 by ANOVA). Simvastatin combined with ramipril significantly improved endothelium-dependent vasodilation and fibrinolysis potential and reduced plasma levels of oxidant stress and inflammation markers in hypercholesterolemic patients.
Hypertension 2004 Aug
PMID:Simvastatin combined with ramipril treatment in hypercholesterolemic patients. 1518 51

Hypertension and diabetes mellitus are closely interrelated and coexist in as many as two-thirds of patients with type 2 diabetes. The consequent risk of such an association is an accelerated development of atherosclerotic cardiovascular disease and nephropathy complications.In choosing an antihypertensive agent, effectiveness needs to be accompanied by favourable metabolic, cardioprotective, and nephroprotective properties. Given the multifactorial nature of hypertension, the approach that has gained widespread agreement is treatment with more than one agent. Agents with different mechanisms of action increase antihypertensive efficacy because of synergistic impacts on the cardiovascular system. Combination therapy allows the use of lower doses of each antihypertensive agent which accounts for the excellent tolerability of combination products.The aim of the present study is to quantify the efficacy of combination therapy of Eprosartan 600 mg respectively Ramipril 5 mg with low-dose Hydrochlorothiazide and Moxonidine on blood pressure levels in patients with essential hypertension and associated diabetes mellitus type 2.The use of monotherapy (Eprosartan or Ramipril) followed by addition of low-dose Hydrochlorothiazide as second agent and of Moxonidine as a third agent will be individualized to the severity of hypertension in the particular patient and to his/her degree of response to current treatment.
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PMID:A novel approach to treatment of hypertension in diabetic patients - a multicenter, double-blind, randomized study comparing the efficacy of combination therapy of Eprosartan versus Ramipril with low-dose Hydrochlorothiazide and Moxonidine on blood pressure levels in patients with hypertension and associated diabetes mellitus type 2 - rationale and design [ISRCTN55725285]. 1546 84

About two thirds of patients on renal replacement therapy irreversibly lose their kidney function because of progressive nephropathies, such as diabetic nephropathy and nondiabetic chronic renal disease. Halting the progression of these patients to end-stage renal disease (ESRD) is instrumental to substantially decrease the need and cost for renal replacement therapy. A large number of experimental studies have demonstrated that chronic nephropathies share common pathogenic mechanisms that contribute to renal disease progression, even independently of the original etiology. Actually, a variety of insults may result in a common pathway of systemic hypertension, increased glomerular pressure and protein ultrafiltration, glomerular and tubular protein overload, chronic inflammation and, ultimately, scarring. Experimental and clinical data converge to indicate that in chronic renal disease increased protein traffic is nephrotoxic, proteinuria predicts disease progression, and proteinuria reduction is renoprotective. Initial clinical trials, mostly in patients with no or mild proteinuria, failed to demonstrate that ACE inhibition therapy is renoprotective in nondiabetic chronic nephropathies. Consistently, meta-analyses based on data generated by these trials failed to detect a specific, blood pressure-independent, renoprotective effect of ACE inhibition therapy. The Ramipril Efficacy In Nephropathy (REIN) study found that ACE inhibitors, by reducing urinary proteins, may contribute to improve the outcome of nondiabetic renal disease, and reduce the risk of progression to ESRD by about 50%. Cumulative meta-analyses, including the REIN study results, confirmed and extended these findings. Thus, well-designed trials in properly selected and carefully monitored study populations continue to be the best approach to test the efficacy of novel treatments. The meta-analyses may help confirming the consistency of these findings and their generalizability to larger cohorts of patients.
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PMID:Proteinuria predicting outcome in renal disease: nondiabetic nephropathies (REIN). 1548 27

Type 2 diabetes mellitus is becoming a major health problem associated with excess morbidity and mortality. As the prevalence of type 2 diabetes is rapidly increasing, prevention of the disease should be considered as a key objective in the near future. Besides lifestyle changes, various pharmacological treatments have proven their efficacy in placebo-controlled clinical trials, including antidiabetic drugs such as metformin, acarbose and troglitazone, or antiobesity agents such as orlistat. Arterial hypertension, a clinical entity in which insulin resistance is common, is strongly associated with type 2 diabetes and may precede the disease by several years. While antihypertensive agents such as diuretics or beta-adrenoceptor antagonists may worsen insulin resistance and impair glucose tolerance, newer antihypertensive agents exert neutral or even slightly positive metabolic effects. Numerous clinical trials have investigated the effects of ACE inhibitors or angiotensin II receptor antagonists (ARAs) on insulin sensitivity in hypertensive patients, with or without diabetes, with no consistent results. Almost half of the studies with ACE inhibitors in hypertensive nondiabetic individuals demonstrated a slight but significant increase in insulin sensitivity as assessed by insulin-stimulated glucose disposal during a euglycaemic hyperinsulinaemic clamp, while the other half failed to reveal any significant change. The effects of ARAs on insulin sensitivity are neutral in most studies. Mechanisms of improvement of glucose tolerance and insulin sensitivity through the inhibition of the renin-angiotensin system (RAS) are complex. They may include improvement of blood flow and microcirculation in skeletal muscles and, thereby, enhancement of insulin and glucose delivery to the insulin-sensitive tissues, facilitating insulin signalling at the cellular level and improvement of insulin secretion by the beta cells. Six recent large-scale clinical studies reported a remarkably consistent reduction in the incidence of type 2 diabetes in hypertensive patients treated with either ACE inhibitors or ARAs for 3-6 years, compared with a thiazide diuretic, beta-adrenoceptor antagonist, the calcium channel antagonist amlodipine or even placebo. The relative risk reduction averaged 14% (p = 0.034) in the CAPPP (Captopril Prevention Project) with captopril compared with a thiazide or beta1-adrenoceptor antagonist, 34% (p < 0.001) in the HOPE (Heart Outcomes Prevention Evaluation) study with ramipril compared with placebo, 30% (p < 0.001) in the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) with lisinopril compared with chlortalidone, 25% (p < 0.001) in the LIFE (Losartan Intervention For Endpoint reduction in hypertension study) with losartan compared with atenolol, and 25% (p = 0.09) in the SCOPE (Study on Cognition and Prognosis in the Elderly) with candesartan cilexetil compared with placebo, and 23% (p < 0.0001) in the VALUE (Valsartan Antihypertensive Long-term Use Evaluation) trial with valsartan compared with amlodipine. All these studies considered the development of diabetes as a secondary endpoint, except the HOPE trial where it was a post hoc analysis. These encouraging observations led to the initiation of two large, prospective, placebo-controlled randomised clinical trials whose primary outcome is the prevention of type 2 diabetes: the DREAM (Diabetes REduction Approaches with ramipril and rosiglitazone Medications) trial with the ACE inhibitor ramipril and the NAVIGATOR (Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research) trial with the ARA valsartan. Finally, ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) will also investigate as a secondary endpoint whether it is possible to prevent the development of type 2 diabetes by blocking the RAS with either an ACE inhibitor or an ARA or a combination of both. Thus, the recent consistent observations of a 14-34% reduction of the development of diabetes in hypertensive patients receiving ACE inhibitors or ARAs are exciting. From a theoretical point of view, they emphasise that there are many aspects of the pathogenesis, prevention and treatment of type 2 diabetes that still need to be uncovered. From a practical point of view, they may offer a new strategy to reduce the ongoing epidemic and burden of type 2 diabetes.
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PMID:Prevention of type 2 diabetes mellitus through inhibition of the Renin-Angiotensin system. 1551 53

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